Supporting play exploration and early developmental intervention versus usual care to enhance development outcomes during the transition from the neonatal intensive care unit to home: a pilot randomized controlled trial

Background While therapy services may start in the Neonatal Intensive Care Unit (NICU) there is often a gap in therapy after discharge. Supporting Play Exploration and Early Development Intervention (SPEEDI) supports parents, helping them build capacity to provide developmentally supportive opportunities starting in the NICU and continuing at home. The purpose of this single blinded randomized pilot clinical trial was to evaluate the initial efficacy of SPEEDI to improve early reaching and exploratory problem solving behaviors. Methods Fourteen infants born very preterm or with neonatal brain injury were randomly assigned to SPEEDI or Usual Care. The SPEEDI group participated in 5 collaborative parent, therapist, and infant interventions sessions in the NICU (Phase 1) and 5 at home (Phase 2). Parents provided daily opportunities designed to support the infants emerging motor control and exploratory behaviors. Primary outcome measures were assessed at the end of the intervention, 1 and 3 months after the intervention ended. Reaching was assessed with the infant supported in an infant chair using four 30 s trials. The Early Problem Solving Indicator was used to evaluate the frequency of behaviors during standardized play based assessment. Effect sizes are including for secondary outcomes including the Test of Infant Motor Performance and Bayley Scales of Infant and Toddler Development. Results No group differences were found in the duration of toy contact. There was a significant group effect on (F1,8 = 4.04, p = 0.08) early exploratory problem-solving behaviors with infants in the SPEEDI group demonstrating greater exploration with effect sizes of 1.3, 0.6, and 0.9 at the end of the intervention, 1 and 3 months post-intervention. Conclusions While further research is needed, this initial efficacy study showed promising results for the ability of SPEEDI to impact early problem solving behaviors at the end of intervention and at least 3 months after the intervention is over. While reaching did not show group differences, a ceiling effect may have contributed to this finding. This single blinded pilot RCT was registered prior to subject enrollment on 5/27/14 at ClinicalTrials.Gov with number NCT02153736

Do hand preferences predict stacking skill during infancy?

The cascade theory of handedness suggests that hand preferences develop from a history of cascading and sequentially developing manual asymmetries for a variety of actions. Infants who consistently use their preferred hand for a variety of actions likely would gain proficiency using that preferred hand and, consequently, perform more proficiently on other challenging manual tasks. One such task is object stacking, which has been linked with a number of cognitive abilities. If infant hand preference facilitates the development of stacking skill, then this could provide a link by which early hand preference might affect the development of cognition. From a sample of 380 infants assessed for an acquisition hand preference across 6-14 months, 131 infants were assessed for stacking skill from 10 to 14 months at monthly visits. Four unique handedness sub-groups were identified from the 380-infant sample: left, trending right, stable right, or no hand preference. Each of the four hand preference groups exhibited different trajectories in the development of their stacking skills. Left- and stable right-handers stacked more items than infants with no preference by 14 months, whereas infants with a trending right preference did not. The proportion of preferred hand use (right and left) from 6 to 9 months also predicted an earlier initial onset of stacking skill, whereas the proportion of only right hand use did not. Thus, the development of a hand preference predicts an earlier emergence of stacking skill and may have implications for other domains of infant cognitive development

Infant Hand Preference and the Development of Cognitive Abilities

Hand preference develops in the first two postnatal years with nearly half of infants exhibiting a consistent early preference for acquiring objects. Others exhibit a more variable developmental trajectory but by the end of their second postnatal year, most exhibit a consistent hand preference for role-differentiated bimanual manipulation. According to some forms of embodiment theory, these differences in hand use patterns should influence the way children interact with their environments, which, in turn, should affect the structure and function of brain development. Such early differences in brain development should result in different trajectories of psychological development. We present evidence that children with consistent early hand preferences exhibit advanced patterns of cognitive development as compared to children who develop a hand preference later. Differences in the developmental trajectory of hand preference are predictive of developmental differences in language, object management skills, and tool-use skills. As predicted by Casasanto’s body-specificity hypothesis, infants with different hand preferences proceed along different developmental pathways of cognitive functioning

The Relation Between Infant Construction Strategy and Language Development in Toddlers

Infants learn from interaction with physical objects in their environments. Object construction, or merging individual objects into a single structure, has been linked previously to language. Items and toys can be structured and combined with similarity to word combinations (Greenfield, 1991). Infants initially combine 2 objects and then graduate on to combine 3 pieces or more. Words are put together in comparable ways, with each word corresponding to an object, and a sentence corresponding to a single structure. The purpose of this project is to explore how construction ability in infants affects language ability in toddlers. We hypothesize that the more advanced the infant’s construction ability at 14 months, the more advanced their language ability will be at 24 months. Methods: At 14 months of age, 47 infants were given 2 sets of nesting cups to assess construction strategy while video-recorded (Greenfield, Nelson, & Saltzman, 1972). Construction strategies coded included “nothing,” (no cup combination), “pairing,” (one cup placed on or inside another cup), and “potting,” (two or more cups placed in or stacked on a third cup). Expressive and receptive language was assessed at 2 years of age using the Preschool Language Scales, 5th edition. Data was analyzed with a regression model, using Hierarchical Linear Modeling 7 (Student version). Results: Infants who combined objects scored higher on expressive language (βs 9.52-14.3, ts(44) 2.19-2.62, ps 0.01-0.03), than infants who did not combine objects at 14 months (β00=92.82). No differences were found for construction strategy and receptive language (βs 5.49-11.79, ts(44) 1.67-0.98, ps \u3e 0.102). Conclusion: The ability to combine cups at 14 months is related to higher expressive language scores. We speculate that the ability to combine toys lays a foundation for combining words into sentences, while language comprehension may originate from other mechanisms. Further studies may assess the number of objects paired successfully and the complexity of construction with success and complexity of sentence structure at different time points throughout early childhood.https://scholarscompass.vcu.edu/uresposters/1217/thumbnail.jp

The influence of a hand preference for acquiring objects on the development of a hand preference for unimanual manipulation from 6 to 14 months

Development of hand preferences for unimanual manipulation of objects was explored in 90 infants (57 males) tested monthly from 6 to 14 months. From a larger sample of 380 infants, 30 infants with a consistent left hand preference for acquiring objects were matched for sex and development of locomotion skills with 30 infants with a consistent right hand preference for acquisition and 30 with no preference. Although frequency of unimanual manipulations increased during 6-14 month period, infants with a hand preference for acquisition did more object manipulations than those without a preference for acquisition. Multilevel modeling of unimanual manipulation trajectories for the three hand-preference groups revealed that hand preferences for unimanual manipulation become more distinctive with age, and the preference is predicted by the hand preference for object acquisition. Infants with a right and left hand preference for object acquisition develop a right and left (respectively) hand preference for unimanual manipulation. However, the majority of infants at each month do not exhibit hand preferences for unimanual manipulation that are unlikely to occur by chance, even by 14 months. The results are consistent with a cascading theory of handedness development in which early preferences (i.e., for acquisition) are transferred to later developing preferences (i.e., for unimanual manipulation)

Cytomegalovirus microRNAs Facilitate Persistent Virus Infection in Salivary Glands

Micro (mi)RNAs are small non-coding RNAs that regulate the expression of their targets' messenger RNAs through both translational inhibition and regulation of target RNA stability. Recently, a number of viruses, particularly of the herpesvirus family, have been shown to express their own miRNAs to control both viral and cellular transcripts. Although some targets of viral miRNAs are known, their function in a physiologically relevant infection remains to be elucidated. As such, no in vivo phenotype of a viral miRNA knock-out mutant has been described so far. Here, we report on the first functional phenotype of a miRNA knock-out virus in vivo. During subacute infection of a mutant mouse cytomegalovirus lacking two viral miRNAs, virus production is selectively reduced in salivary glands, an organ essential for virus persistence and horizontal transmission. This phenotype depends on several parameters including viral load and mouse genetic background, and is abolished by combined but not single depletion of natural killer (NK) and CD4+ T cells. Together, our results point towards a miRNA-based immunoevasion mechanism important for long-term virus persistence

Degradation of cellular mir-27 by a novel, highly abundant viral transcript is important for efficient virus replication in vivo.

Cytomegaloviruses express large amounts of viral miRNAs during lytic infection, yet, they only modestly alter the cellular miRNA profile. The most prominent alteration upon lytic murine cytomegalovirus (MCMV) infection is the rapid degradation of the cellular miR-27a and miR-27b. Here, we report that this regulation is mediated by the ∼1.7 kb spliced and highly abundant MCMV m169 transcript. Specificity to miR-27a/b is mediated by a single, apparently optimized, miRNA binding site located in its 3'-UTR. This site is easily and efficiently retargeted to other cellular and viral miRNAs by target site replacement. Expression of the 3'-UTR of m169 by an adenoviral vector was sufficient to mediate its function, indicating that no other viral factors are essential in this process. Degradation of miR-27a/b was found to be accompanied by 3'-tailing and -trimming. Despite its dramatic effect on miRNA stability, we found this interaction to be mutual, indicating potential regulation of m169 by miR-27a/b. Most interestingly, three mutant viruses no longer able to target miR-27a/b, either due to miRNA target site disruption or target site replacement, showed significant attenuation in multiple organs as early as 4 days post infection, indicating that degradation of miR-27a/b is important for efficient MCMV replication in vivo

Transcriptional Activation of the Adenoviral Genome Is Mediated by Capsid Protein VI

Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral defense mechanisms. The cellular transcriptional repressor Daxx prevents viral gene expression through the assembly of repressive chromatin remodeling complexes targeting incoming viral genomes. However, it has remained unclear how initial transcriptional activation of the adenoviral genome is achieved. Here we show that Daxx mediated repression of the immediate early Ad E1A promoter is efficiently counteracted by the capsid protein VI. This requires a conserved PPxY motif in protein VI. Capsid proteins from other DNA viruses were also shown to activate the Ad E1A promoter independent of Ad gene expression and support virus replication. Our results show how Ad entry is connected to transcriptional activation of their genome in the nucleus. Our data further suggest a common principle for genome activation of DNA viruses by counteracting Daxx related repressive mechanisms through virion proteins

The trace fossil Lepidenteron lewesiensis: a taphonomic window on diversity of Late Cretaceous fishes

The trace fossil Lepidenteron lewesiensis (Mantell 1822) provides an exceptional taphonomic window to diversity of fishes as shown for the Upper Cretaceous of Poland, in the Middle Turonian–Lower Maastrichtian deposits of the Opole Trough, Miechów Trough, Mazury-Podlasie Homocline, and SE part of the Border Synclinorium. Lepidenteron lewesiensis is an unbranched burrow lined with small fish scales and bones, without a constructed wall. It contains scales, vertebrae, and bones of the head belonging to ten taxa of teleostean fishes: two undetermined teleosteans, six undetermined Clupeocephala, one Dercetidae, and one undetermined euteleostean. The preservation of fish remains suggests that fishes were pulled down into the burrow by an animal, probably by eunicid polychaetes.Das Spurenfossil Lepidenteron lewesiensis (Mantell 1822) ermöglicht einen biostratinomischen Einblick in die Diversität von Fischen, wie Fossilmaterial aus der Oberkreide von Polen zeigt. Es stammt aus dem Mittelturonium bis Untermaastrichtium des südöstlichen Abschnittes der Grenz-Synklinale, dem Opolen-Trog, dem Miechów-Trog und der Masuren-Podlachien-Homoklinale. L. lewesiensis ist ein unverzweigter Grabgang ohne ausgekleidete Wände, dessen Ränder von kleinen Fischschuppen und—knochen gebildet werden. Diese setzen sich aus Schuppen, Wirbel und Schädelknochen von zehn Teleostei-Taxa zusammen und zwar aus zwei unbestimmte Teleosteer, sechs unbestimmten Clupeocephala, einem Dercetidae und einem unbestimmten Euteleostei. Die Erhaltung der Fischüberreste deutet darauf hin, dass die Fische von einem Tier, wahrscheinlich einem Polychaeten der Familie Eunicidae, in den Bau gezogen wurden.We are very grateful to Dr. Lionel Cavin (Geneva) and the anonymous reviewer for constructive comments on an earlier version of the manuscript. Additional support was provided by the Jagiellonian University (DS funds), National Science Center (Grant Number: PRO-2011/01/N/ST10/07717), and the Laboratory of Geology (University of Lodz) BSt Grant No. 560/844. We are grateful to Dr. Johann Egger (Wien) and Kilian Eichenseer M.Sc. (Erlangen) for help with translating the abstract into German. We are grateful to Dr. Ursula Göhlich (Wien) for access to the Dercetis specimen